2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multi-criterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSIONS: The new classification criteria, developed using a data-driven and decision-analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSION: The new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout.

New gout test: enhanced ex vivo cytokine production from PBMCS in common gout patients and a gout patient with Kearns-Sayre syndrome.

Monosodium urate (MSU) monohydrate crystals synergize with various toll-like receptor (TLR) ligands to induce interleukin-(IL)-1ß production. Data are shown from a young male with mitochondriopathy in Kearns-Sayre syndrome (KSS) who developed gout and underwent urate-lowering therapy (ULT) versus a group of common gout patients. Peripheral blood mononuclear cells (PBMCs) are exposed in vitro to MSU crystals in the presence/absence of TLR2 ligands palmitic acid (C16:0) or palmitoyl-3-cysteine (Pam3Cys); proinflammatory cytokine production (IL-1ß, IL-6, IL-8) is assessed by specific ELISA's. MSU crystals alone failed to induce IL-1beta, IL-6, or IL-8 in both the KSS patient and gout controls. A strong synergy between MSU crystals and C16:0 or Pam3Cys for induction of IL-1 beta/IL-6 is found in gout patients, but in gout with KSS, we found even more response than in control gout patients. Pam3Cys exposure reveals an enhanced response in cells originating from the KSS patient, indicating a high producer phenotype in response to TLR2 stimulation. During ULT, serum urate levels dropped in the KSS case. The hyperresponse of TLR2 may be secondary to the high serum urate concentration of 0.92 mmol/l that was initially found in circulation in vivo. Within a 6-month period, the serum urate concentration dropped, and the in vitro stimulation tests improved but did not fully normalize yet. The ex vivo cytokine production in gout patients is promising a novel gout test; PBMCs' responses in the mitochondriopathic gout patient is enhanced when compared with common gout patients, indicating a supersensitive gout patient profile. The non-inflammatory presentation in the KSS case with bulky gout is due to less inflammatory MSU crystals, i.e., specific crystal stereochemical/conformational properties. For developing gout attacks, the serum urate level and specific crystal properties both are of importance. Key Messages 1. Ex vivo cell tests are promising to serve as a novel gout lab test for screening purposes. 2. Ex vivo cellular responses are reduced following intraarticular glucocorticoid injection and/or urate-lowering therapy. 3. Crystal conformation properties play a role in the inflammatory in vivo and ex vivo response in gout. 4. A young male with Kearns-Sayre syndrome is described with less pronounced inflammatory PMBC responses to his own MSU crystals which explains the advanced stage of urate accumulation in this individual.